These include (i) decreased or absent antigen expression [e.g., tumor antigens, MHC I receptors, MHC I chain-related gene A and B (MICA and MICB)]; (ii) changes in the expression of cell receptors (e.g., tumor-expressed markers, PD-1/PD-L1, CTLA-4, among other ICPs); and (iii) alterations in cellular enzymes and metabolic pathways [e.g., CD38/NAD+glycohydrolase; indoleamine 2,3-dioxygenase (IDO)] (37, 117) are the most likely involved in changes within the TME, resulting in a lack of response to immunotherapy (109). The gene discussed is IDO2; the disease is neoplasm.